Key points

Introduction

CHs are tumors that have a benign histopathology but exhibit aggressive clinical behavior with invasive and metastatic potential. CHs are challenging tumors to treat, and there are still many questions especially about their optimum treatment. In the best cases, recurrence is delayed, but it is inevitable after 10 or 20 years. However, important improvements have been made over the past decade. First, with the advances of new techniques such as endoscopic endonasal approach (EEA) of skull base (SB) CH, the extent of surgical resection has improved, which has tremendous importance because complete tumor removal is still the most important prognostic factor. Second, complementary targeted chemotherapy is being developed based on a better knowledge of the signaling pathways involved in the oncogenesis of CHs.

Introduction

CHs are tumors that have a benign histopathology but exhibit aggressive clinical behavior with invasive and metastatic potential. CHs are challenging tumors to treat, and there are still many questions especially about their optimum treatment. In the best cases, recurrence is delayed, but it is inevitable after 10 or 20 years. However, important improvements have been made over the past decade. First, with the advances of new techniques such as endoscopic endonasal approach (EEA) of skull base (SB) CH, the extent of surgical resection has improved, which has tremendous importance because complete tumor removal is still the most important prognostic factor. Second, complementary targeted chemotherapy is being developed based on a better knowledge of the signaling pathways involved in the oncogenesis of CHs.

Definition

CHs are gelatinous (jellylike), grayish, and more or less encapsulated and infiltrative tumors originating from extradural vestiges of the notochord (NC). The NC is the primary axis of the embryo along which are organized the neuraxis, the spinal axis, and the SB up to the dorsum sellae. The NC runs from the sacrum (S) all along the spine, across the vertebral bodies up to the odontoid process and the lower clivus where it crosses the bone (mediobasal canal) to reach the pharynx; it then runs into the pharyngeal soft tissues, in front of the clivus to its upper limit where it crosses again the bone and ends its course at the top of the dorsum sellae ( Fig. 1 ). The NC starts to regress on the sixth or seventh week and completely disappears during the first years of life. The last remnant of the NC is the nucleus pulposus of the intervertebral disks, but it cannot be considered as a possible origin of CHs. In fact, intervertebral disks are never involved in CHs even in the case of multiple vertebrae invasion. Moreover, CHs are found in structures without disks such as the clivus or the S. Therefore the last remnants must be distinguished from the vestiges of NC, the latter being the only true origin of CHs. One of these vestiges is well known and was discovered by Luschka (1856) and Virchow (1857); it first was erroneously called ecchondrosis physaliphora because it was supposed to be of cartilaginous origin. The origin of this vestige from the NC was established by Muller in 1858 and linked to CHs only in 1895 by Ribbert. Since then, it is named ecchordosis physaliphora (EP). The EP is a small (<1 cm) round mass located behind the clivus (sometimes connected to it by a pedicle) in the prepontine area and observed in 0.4% to 2% of the cases at autopsy or on MRI ( Fig. 2 ). Another likely vestige is called benign notochord cell tumor (BNCT); it is most commonly described in vertebral bodies and sometimes in association with true CHs. Yamaguchi and colleagues found 20 BNCTs in different locations from 100 autopsies. BNCTs present on MRI as noninvasive and nondestructive nodular lesions with signal similar to that of CHs on T1 and T2 sequences but without contrast enhancement. EP and BNCT are generally asymptomatic or only associated with local pain ( Table 1 ).

Scheme of the upper part of the NC course.

T2 MRI sequence in sagittal view showing a prepontine EP connected to the clivus. Arrow indicates the part of the lesion into the clivus. Arrowhead indicates prepontine EP.

Positive diagnosis

CHs exhibit particular but not specific features on computed tomography and MRI ( Figs. 3 and 4 ) : essentially destructive and invasive aspects with hyposignal in T1 sequences, hypersignal in T2 sequences, and contrast enhancement. Rather than calcifications, bony remnants can be seen inside the tumors ( Fig. 5 ).

T1 MRI sequences with contrast of CH at the craniocervical junction ( A ) and at the upper clivus ( B ). Arrow indicates the part of the lesion into the clivus. Arrowhead indicates prepontine EP.

( A , B ) Computed tomographic axial views of a small clival CH.

Axial T1 ( A ), T2 ( B ), and T1 with contrast ( C ) MRI sequences at the midclivus with intradural ( arrow ) extension, Hyposignal T1 zone ( asterik ), Hyposignal septa ( arrowhead ).

Histology is also particular with largely vacuolated cells called physaliphora cells surrounded by a myxoid matrix. There are 3 histologic types of CHs: classical, chondroid with a partially chondroid matrix, and dedifferentiated (or sarcomatous). In the dedifferentiated type, there are areas with classic features of CHs and other parts with features of sarcomas.

CHs are mainly confused with chondrosarcomas on radiologic diagnosis, which have similar radiological features but harbor more frequently true calcifications. Histologic aspects may also be confusing, but nowadays, immunohistology allows a clear differentiation. The most specific and sensitive markers are cytokeratins and brachyury. Brachyury is a protein linked with a specific gene locus (6q27) and is an intranuclear transcription factor without which the development of the NC is abnormal. Brachyury is always found in any tissue or lesion that is derived from the NC including CHs, EP, and BNCTs, as well as in the NC itself. However, it is not found in the nucleus pulposus. This protein is also present in hemangioblastomas and in few testicular tumors. Brachyury may also be present in some tumors called parachordomas, that are very similar to CHs but located outside of the NC axis, most commonly in the limbs. In the last literature review by Clabeaux and colleagues (2008), 45 cases were reported located in any part of the body. However, Tirabosco and colleagues (2008) found only 10 cases positive for brachyury and suggested to call them extra-axial CHs. Only brachyury-negative tumors should be named parachordomas; they have been included by the World Health Organization in the group of mixed tumors and myoepitheliomas.

Tests for brachyury yield positive results homogeneously in every part of a CH, except in the sarcomatous part of the dedifferentiated CHs.

Epidemiology

CHs account for 1.4% of all primary malignant bone tumors, 0.4% of all intracranial tumors, 0.2% of SB tumors, and 17% of primary bone tumors of the spine, most commonly at the C1-C2 level.

In an American register (McMaster and colleagues ) collecting 400 cases over 22 years, CHs were observed in 0.8 of 1,000,000 people and were equally distributed between the three most frequent location of chordomas: 29.2% in the S, 32% in the SB, and 32.8% in the mobile spine (MS) ( Figs. 6 and 7 ); SB location is more frequent in females (39%). CH occurs predominantly in males (60%), and the median age is 58.5 years. Patients with SB CHs are younger than those with S and MS CHs (49 vs 69 years).

Sagittal ( A ) and coronal ( B ) T1 ( A ) and T2 ( B ) MRI sequences of a cervical spine CH. Arrows indicate the part of the lesion into the clivus. Arrowhead indicates prepontine EP.

Sagittal T1 ( A ) and T2 ( B ) MRI sequences of a sacral CH. Hyposignal T1 zone ( Asterik ), Hyposignal septa ( arrow ).

Particular forms

The course of the NC explains that CHs can be observed in the pharynx without any bone involvement. On the contrary, location away from the midline can only be explained by an NC forking ; jugular foramen location has been reported in 9 cases and location in Meckel cave has been reported in 5.

Most CHs are located extradurally at least at the beginning of their evolution ( Fig. 8 ); after some time, they may rupture the dura and extend into the intradural (ID) space ( Fig. 9 ); ID CHs often remain subdural, and true subarachnoid extension and even pia mater infiltration are rare and occur more frequently at the time of recurrence. Some rare CHs are initially located in the ID space mostly in the prepontine area but this is not the only location. In the literature, 34 ID cases were reported: 19 prepontine, 6 in the sellar region, 2 in the foramen magnum, 1 in the cerebellopontine angle, 1 in the Meckel cave, 4 cervical, and 1 thoracic. When they are small, these ID CHs may be confused with EP; like any proliferative CH, ID CHs show contrast enhancement on MRI and have a myxoid matrix, whereas EP do not (as well as BNCTs). However, both yield positive results for brachyury (see Table 1 ).

Sagittal ( A ) and axial ( B ) T2 MRI sequences of an entirely extradural CH of the upper clivus. Arrows indicate the part of the lesion into the clivus. Arrowheads indicate prepontine EP.

Axial T2 MRI sequence of a clival CH with intradural extension ( arrowhead ); notice the displacement and the encasement of the basilar trunk. Basilar artery embedded into the tumor ( arrow ).

CHs located inside the brain parenchyma were also observed in 4 cases, 1 hypothalamic, 1 cerebellar, 1 pineal, and 1 on both sides of the tentorium. However, in these old reports, there is no immunohistological study.

Familial forms and associations

Eleven families presenting with at least 2 CHs in the family (46 cases) have been reported. CHs were most commonly located in the SB. Several studies showed mutations in different genes; the most convincing study found an alteration of the locus 6q27 (the brachyury locus) with the same modification being observed in all affected members in 4 of 7 families.

Several associations of CHs with another pathologic condition have been described. Tuberous Sclerosis Complex (TSC) is the most interesting because this disease is due to inactivation of a suppressor gene that induces activation of mammalian target of rapamycin (mTOR) (transduction factor) and so stimulates tumor growth and proliferation. In the 10 published cases, the mean age was very less (6.2 months), there were 4 sacral CHs, and the prognosis was rather good (83% survival at 5 years).

Associations with Ollier disease, Maffucci syndrome, and Crohn disease suggest a gene modification but only a few cases have been published. Association with sellar pathologies (Rathke cleft cyst and Cushing syndrome) may be explained by the course of NC that ends at this level.

Treatment modalities

Surgery is the most efficient treatment because complete resection remains the most important prognostic factor. Considering the midline location of CH and the initial bone and extradural location, anterior approaches that do not cross the cranial nerves (CNs) and vessels are the most logical and should be favored. For long, transoral, transsphenoidal, and transfacial routes were used. Nowadays, EEAs are supplanting all of them. Using the endoscope, it is possible to reach any part of the clivus from the dorsum sellae (with pituitary transposition) to its lower tip and even the craniocervical junction (CCJ). Lateral limits of the approach are venous structures (cavernous sinus and jugular bulb), CNs and arteries (carotid and vertebral arteries). However, it is now possible for experienced teams to reach the lateral SB and to control and work around these vessels and CNs with an acceptable risk. Micro-Doppler and neuronavigation are mandatory in those situations as well as in recurrent CHs. Monitoring of the CNs, especially the sixth and twelfth, also brings safety in the surgical resection. Balloon occlusion tests (BOTs) may also be a safe preoperative option, leading occasionally to a preoperative or Intra-operative occlusion. In the authors’experience, BOT was performed in 40 cases (33%) and the carotid and vertebral arteries were occluded, respectively, in 5 and 11 cases without complications ( Table 2 ). One of the main issue with endoscopic techniques is the dural closure in case of ID extension (more than 50% of the authors’ 128 cases). Recurrent cases are even more challenging to close because the nasoseptal flap that is the keystone of a successful closure may not be available anymore. In these recurrences, previous radiation therapy also increases the risk of cerebrospinal fluid (CSF) leak. If no other option for closure is available, the temporoparietal fascia flap can be a life-saving option for the patient. Despite recent improvements in closure techniques, the rate of postoperative CSF leak is still around 10%.

Table 2

Lariboisière series

	Total	Clivus	CCJ	Cervical Spine
Number	128	58	47	23
Age (y)	43	46	36	44
ID/ED (%)	53	65	49	27
Secondary patients (%)	36	23	45	57
Combined approaches (%)	29.5	32.5	25.5	26
BOT (occlusion)	40 (16)	18 (5 ICA)	18 (6 VA)	4 (5 VA)
RxTT (Proton), %	81 (79)	79 (93)	86 (68.5)	79 (60)

Only gold members can continue reading. Log In or Register to continue

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on Facebook (Opens in new window)

Related

Related posts:

Endoscopic Endonasal Skull Base Surgery Endoscopic Endonasal Extended Approaches for the Management of Large Pituitary Adenomas Endoscopic Endonasal Repair of Spontaneous and Traumatic Cerebrospinal Fluid Rhinorrhea Surgical Techniques for Sinonasal Malignancies Endoscopic Endonasal Approach to Ventral Posterior Fossa Meningiomas Endoscopic Endonasal Odontoidectomy

Stay updated, free articles. Join our Telegram channel

Join